Mutations in K-Ras, part of the RAS family of small GTPases, are among the most frequent oncogenic drivers in human cancers, with significant incidence in pancreatic, colorectal, and non-small cell lung cancers. These mutations cause continuous activation of critical signaling pathways, such as MAPK and PI3K-AKT, resulting in unchecked cellular proliferation, metabolic changes, and resistance to apoptosis. An integral upstream regulator of K-Ras function is the epidermal growth factor receptor (EGFR), which, in normal conditions, activates RAS proteins. However, mutated K-Ras becomes perpetually active and does not respond to typical EGFR inhibition, posing challenges in treating receptor-involved cancers like colorectal cancer and NSCLC. The persistent label of K-Ras as an “undruggable” target is now being challenged by breakthroughs in small-molecule inhibitors, synthetic lethality, and immunotherapeutic tactics, necessitating deeper exploration into its regulation and signaling cross-talk for more effective treatments.
This Research Topic aims to collect pioneering research and reviews that delve into the molecular processes by which K-Ras mutations induce oncogenesis, variable signaling dynamics depending on cancer type, and cutting-edge strategies to target the K-Ras pathway and its vulnerabilities. Key objectives include clarifying the interactions between oncogenic K-Ras and various upstream factors, examining its effects on downstream signaling pathways, and evaluating its influence on tumor metabolism, immunity, and metastasis to develop advanced therapeutic strategies.
To gather further insights in K-Ras pathway targeting, we welcome articles addressing, but not limited to, the following themes:
o Functional implications of oncogenic K-Ras mutations in various cancer backgrounds
o Interactions with upstream activators, including EGFR, HER2, SHP2, or SOS1
o Modulation of MAPK, PI3K-AKT, RAL-GDS, and other pathways by K-Ras
o Mechanisms of resistance and feedback in K-Ras-driven malignancies
o Interaction between K-Ras signaling and the tumor microenvironment
o K-Ras's role in cancer metabolism, immune evasion, and metastasis
o Innovative small-molecule inhibitors and synthetic lethality strategies targeting K-Ras
o Immunotherapeutic approaches modifying K-Ras-associated pathways
o Biomarkers predictive of responses to K-Ras-focused therapies
Accepted article types include Original Research, Reviews, Perspectives, and Hypothesis and Theory. This collection will consolidate new understandings of K-Ras-related cancer biology and resistance, enhancing translational initiatives to improve therapeutic outcomes for patients facing K-Ras-mutant cancers.
Please note that manuscripts consisting solely of bioinformatics or computational analysis of public omics databases that are not supplemented by relevant functional validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this Research Topic.
Article types and fees
This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:
Case Report
Clinical Trial
Community Case Study
Editorial
FAIR² Data
Hypothesis and Theory
Methods
Mini Review
Opinion
Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.
Article types
This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:
Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
